Cell type- and developmental stage-specific activation of NF-kappaB by fMet-Leu-Phe in myeloid cells

Chemoattractants induce a variety of phagocytic functions including transendothelial migration, degranulation, and the generation of superoxide anions. We report here that the prototypic chemotactic peptide fMet-Leu-Phe (fMLF) stimulates the activation of nuclear factor-kappaB (NF-kappaB), a transcription factor that is central to the regulation of proinflammatory immediate-early gene expression. In freshly prepared peripheral blood mononuclear cells, fMLF (1-100 nM) induced a kappaB binding activity that was receptor-dependent and involved the p50 and p65 subunits of the NF-kappaB/Rel family of proteins. The activation of NF-kappaB by fMLF appeared to be cell-specific and different from the activation of NF-kappaB by tumor necrosis factor-alpha (TNFalpha). Neutrophil preparations that responded to fMLF, TNFalpha, and lipopolysaccharides with interleukin-8 secretion did not show NF-kappaB activation, whereas N-formyl peptide receptor (FPR)-transfected HL-60 cells were responsive to TNFalpha but not fMLF for NF-kappaB activation. Differentiation of FPR-transfected HL-60 cells with dimethyl sulfoxide for 3-5 days conferred the capability of the cells to activate NF-kappaB in response to fMLF without a significant increase in the amount of FPR. These results identify NF-kappaB as a transcription factor that can be activated by the prototypic chemotactic peptide and demonstrate that this function is both highly regulated and dependent on signaling components specifically expressed during myeloid differentiation.